title: Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival.
abstract: B23/NPM is a major nucleolar phosphoprotein that has a critical role in cell proliferation and cell death. Here, we show that it forms a complex with Akt on growth factor (GF) stimulation in both the cytoplasm and the nucleus, for which Akt activation is indispensable. The C terminus of B23 (239-294 residues) potently binds pleckstrin homology (PH) domain of Akt. Akt binding to B23 protects it from proteolytic degradation by caspase-3, leading to the up-regulation of cell survival. Interestingly, unsumoylated B23 K263R, but not wild-type B23, strongly interacts with Akt in the nucleoplasm in the absence of GFs. Furthermore, we show that Akt2, but not other isoforms, specifically regulates B23 sumoylation and protein stability. Also, nuclear Akt regulates the cell cycle progression activity of B23. Therefore, our findings support that nuclear Akt binds and stabilizes B23 in the nucleoplasm, and regulates its activities in cell survival and cell cycle.
authors.affiliation: Departments of Molecular Cell Biology and Anatomy and Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Lee
authors.forename: Truong L
authors.initials: TL
authors.lastname: Xuan Nguyen
authors.forename: Joung Woo
authors.initials: JW
authors.lastname: Choi
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Lee
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Zhixue
authors.initials: Z
authors.lastname: Liu
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
authors.forename: Jee-Yin
authors.initials: JY
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001665:Binding Sites; D053148:Caspase 3 / Q000378:metabolism*; D002453:Cell Cycle; D002467:Cell Nucleus; D002470:Cell Survival; D003593:Cytoplasm; D006624:Hippocampus; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D000090243:Nucleophosmin; D016716:PC12 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D054875:Ubiquitination
chemical_list: D009687:Nuclear Proteins; D000090243:Nucleophosmin; C494923:Akt2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3